800 pts were randomized to ENZA & 399 to PBO. ∼30% of pts in each arm were on CS at baseline. Multivariate analysis showed baseline oral CS use was associated with the OS outcome, with median OS of 11 mo (95% CI: 10, 13) for pts on CS vs median OS not met (18, NM) for pts not on baseline CS (HR = 0.54; 95% CI: 0.45, 0.64)). Subgroup analysis showed for pts on CS median OS was 12.3 mo on ENZA vs 9.3 mo on PBO (P = 0.0116, HR 0.70) and for pts not on CS median was not met on ENZA vs 15.8 mo on PBO (P < 0.0001, HR 0.59). ENZA was also consistently superior to PBO on rPFS and TTPP, regardless of baseline
CS use.

Results of Stepwise Multivariate Analysis of Overall Survival

Variable

Parameter Estimates

HR for Death (95% CI)

Coefficient

P-value

Treatment (ENZA vs PBO)

-0.54 ± 0.090

<0.0001

0.58 (0.49-0.70)

Mean pain score:
<4 vs. ≥4

-0.25 ± 0.098

0.0091

0.78 (0.64-0.94)

Progression at study entry: PSA only vs radiographic

-0.35 ± 0.094

0.0002

0.70 (0.59-0.85)

Visceral disease at screening (No vs Yes)

-0.42 ± 0.097

<0.0001

0.66 (0.54-0.80)

Baseline hemoglobin

-0.03 ± 0.003

<0.0001

0.97 (0.97-0.98)

Baseline lactate dehydrogenase (LDH)

0.002 ± 0.000

<0.0001

1.002 (1.001-1.002)

Baseline corticosteroid use (No vs Yes)

-0.62 ± 0.091

<0.0001

0.54 (0.45-0.64)

1. Survival for pts who had not died by the time of analysis was censored at the date the pt was last known to be alive. 2. confidence interval

Conclusions

Use of CS at baseline was associated with reduced OS in the multivariate model. This finding should be further explored in future studies. While pts on baseline CS had worse outcomes, ENZA was consistently superior to PBO on OS, rPFS, and TTPP regardless of baseline CS use.